α-Tocopherol-loaded niosome prepared by heating method and its release behavior.

α-Tocopherol-loaded niosome was developed using modified heating method. The influence of surfactants (Span60 and Tween60) in different mole ratios, presence or absence of cholesterol (Chol) and dicetyl phosphate (DCP) as well as different concentration of α-tocopherol (α-TOC) on mean size, polydispersity index, zeta potential and entrapment efficiency (EE) was evaluated. The results showed that α-TOC loaded niosomes exhibited a small mean size (73.85±0.6-186±0.58nm), narrow size distribution and high EE (61.13±0.52-98.92±0.92). By decreasing the HLB, the EE and stability of the niosomes increased. The DCP and Chol improved the physicochemical properties of niosomes. 3:1 mole ratio of Span 60:Tween 60, 4mg/ml of α-TOC and 25:12.5:2.5 mole ratio of surfactant:Chol:DCP was the optimum formulation in the encapsulation of α-TOC applying niosome system. The niosomes had sustained release profile in the simulated gastric and intestinal fluid.

Novel 5'TOPmRNAs regulated by ribosomal S6 kinase are important for cardiomyocyte development: S6 kinase suppression limits cardiac differentiation and promotes pluripotent cells toward a neural lineage.

Moving stem cells from bench to bedside has been a challenging task. Undermining this task is comprehending and optimizing the underlying regulatory mechanisms that drive differentiation of stem cells into desired cell and tissue types. Here we present evidence that ribosomal S6 kinase (S6K) is among the proteins upregulated as embryonic stem cells (ESCs) and human induced pluripotent stem cells differentiate into beating cardiomyocytes. We hypothesized that S6K plays a pivotal role in cardiomyogenesis, primarily because it regulates the translation of 3 cardiac-involved genes recently shown to have 5' terminal oligopyrimidine (5'TOP) sequences: connexin 43 (Cx43), desmoplakin (Dsp), and phosphatase and tensin homolog (PTEN). Along with another independent laboratory, we confirmed that S6K is indeed upregulated in beating ESC-derived cardiomyocytes compared to the surrounding nonbeating, differentiated cells. S6K short interfering RNA-transfected stem cell cultures indicate that inhibition of S6K strongly hinders development of cardiomyocyte beating and translation of Cx43, Dsp, and PTEN; these cardiac 5'TOP mRNAs were only properly translated in cells with S6K, supporting our hypothesis. An unexpected discovery took the role of S6K one step further: S6K-knockdown stem cell cultures developed significantly more neurons than seen in embryoid bodies subjected to a typical cardiac differentiation protocol. These results introduced the novel idea that in addition to its critical cardiac roles, S6K may be a significant factor that prevents stem cells from pursuing a neuronal pathway. Overall, results have indicated the necessity of S6K for normal stem cell cardiomyogenesis, as well as lowered S6K expression for stem cell neurogenesis.